Bis(5'-Adenosyl)-Triphosphatase (FHIT) Human Recombinant Protein

Cleaves P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to yield AMP and ADP. Can also hydrolyze P(1)-P(4)-bis(5'-adenosyl) tetraphosphate (Ap4A), but has extrely low activity with ATP. Modulates transcriptional activation by CTNNB1 and thereby contributes to regulate the expression of genes essential for cell proliferation and survival, such as CCND1 and BIRC5. Plays a role in the induction of apoptosis via SRC and AKT1 signaling pathways. Inhibits MDM2-mediated proteasomal degradation of p53/TP53 and thereby plays a role in p53/TP53-mediated apoptosis. Induction of apoptosis depends on the ability of FHIT to bind P(1)-P(3)-bis(5'-adenosyl) triphosphate or related compounds, but does not require its catalytic activity, it may in part come from the mitochondrial form, which sensitizes the low-affinity Ca2+ transporters, enhancing mitochondrial calcium uptake. Functions as tumor suppressor

The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers.Ohta M., Inoue H., Cotticelli M.G., Kastury K., Baffa R., Palazzo J., Siprashvili Z., Mori M., McCue P., Druck T., Croce C.M., Huebner K.Cell 84:587-597(1996) Structure and expression of the human FHIT gene in normal and tumor cells.Druck T., Hadaczek P., Fu T.B., Ohta M., Siprashvili Z., Baffa R., Negrini M., Kastury K., Veronese M.L., Rosen D., Rothstein J., McCue P., Cotticelli M.G., Inoue H., Croce C.M., Huebner K.Cancer Res. 57:504-512(1997) Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism.Corominas R., Yang X., Lin G.N., Kang S., Shen Y., Ghamsari L., Broly M., Rodriguez M., Tam S., Wanamaker S.A., Fan C., Yi S., Tasan M., Lemmens I., Kuang X., Zhao N., Malhotra D., Michaelson J.J., Vacic V., Calderwood M.A., Roth F.P., Tavernier J., Horvath S., Salehi-Ashtiani K., Korkin D., Sebat J., Hill D.E., Hao T., Vidal M., Iakoucheva L.M.Nat. Commun. 5:3650-3650(2014) Mutational analysis of FHIT gene.Naqvi S.R.A., Malik A., Kukreti H., Chaudhary A., Anand R., Deo S.S., Shukla N.K., Husain S.A., Pasha S.T.Complete sequencing and characterization of 21,243 full-length human cDNAs.Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.Nat. Genet. 36:40-45(2004) Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Fhit, a putative tumor suppressor in humans, is a dinucleoside 5',5''-P1,P3-triphosphate hydrolase.Barnes L.D., Garrison P.N., Siprashvili Z., Guranowski A., Robinson A.K., Ingram S.W., Croce C.M., Ohta M., Huebner K.Biochemistry 35:11529-11535(1996) The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8.Gemmill R.M., West J.D., Boldog F., Tanaka N., Robinson L.J., Smith D.I., Li F., Drabkin H.A.Proc. Natl. Acad. Sci. U.S.A. 95:9572-9577(1998) Association of FHIT (fragile histidine triad) , a candidate tumour suppressor gene, with the ubiquitin-conjugating enzyme hUBC9.Shi Y., Zou M., Farid N.R., Paterson M.C.Biochem. J. 352:443-448(2000) Designed FHIT alleles establish that Fhit-induced apoptosis in cancer cells is limited by substrate binding.Trapasso F., Krakowiak A., Cesari R., Arkles J., Yendamuri S., Ishii H., Vecchione A., Kuroki T., Bieganowski P., Pace H.C., Huebner K., Croce C.M., Brenner C.Proc. Natl. Acad. Sci. U.S.A. 100:1592-1597(2003) The mechanism of action of the fragile histidine triad, Fhit isolation of a covalent adenylyl enzyme and chemical rescue of H96G-Fhit.Huang K., Arabshahi A., Wei Y., Frey P.A.Biochemistry 43:7637-7642(2004) Synergistic tumor suppression by coexpression of FHIT and p53 coincides with FHIT-mediated MDM2 inactivation and p53 stabilization in human non-small cell lung cancer cells.Nishizaki M., Sasaki J., Fang B., Atkinson E.N., Minna J.D., Roth J.A., Ji L.Cancer Res. 64:5745-5752(2004) Fhit is a physiological target of the protein kinase Src.Pekarsky Y., Garrison P.N., Palamarchuk A., Zanesi N., Aqeilan R.I., Huebner K., Barnes L.D., Croce C.M.Proc. Natl. Acad. Sci. U.S.A. 101:3775-3779(2004) Fhit modulation of the Akt-survivin pathway in lung cancer cells Fhit-tyrosine 114 (Y114) is essential.Semba S., Trapasso F., Fabbri M., McCorkell K.A., Volinia S., Druck T., Iliopoulos D., Pekarsky Y., Ishii H., Garrison P.N., Barnes L.D., Croce C.M., Huebner K.Oncogene 25:2860-2872(2006) The tumor suppressor Fhit acts as a repressor of beta-catenin transcriptional activity.Weiske J., Albring K.F., Huber O.Proc. Natl. Acad. Sci. U.S.A. 104:20344-20349(2007) Intramitochondrial calcium regulation by the FHIT gene product sensitizes to apoptosis.Rimessi A., Marchi S., Fotino C., Romagnoli A., Huebner K., Croce C.M., Pinton P., Rizzuto R.Proc. Natl. Acad. Sci. U.S.A. 106:12753-12758(2009) Initial characterization of the human central proteome.Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.BMC Syst. Biol. 5:17-17(2011) MAD analysis of FHIT, a putative human tumor suppressor from the HIT protein family.Lima C.D., D'Amico K.L., Naday I., Rosenbaum G., Westbrook E.M., Hendrickson W.A.Structure 5:763-774(1997) Structure-based analysis of catalysis and substrate definition in the HIT protein family.Lima C.D., Klein M.G., Hendrickson W.A.Science 278:286-290(1997) Genetic, biochemical, and crystallographic characterization of Fhit-substrate complexes as the active signaling form of Fhit.Pace H.C., Garrison P.N., Robinson A.K., Barnes L.D., Draganescu A., Roesler A., Blackburn G.M., Siprashvili Z., Croce C.M., Huebner K., Brenner C.Proc. Natl. Acad. Sci. U.S.A. 95:5484-5489(1998)

Small volumes of FHIT recombinant protein vial(s) may occasionally become entrapped in the seal of the product vial during shipment and storage. If necessary, briefly centrifuge the vial on a tabletop centrifuge to dislodge any liquid in the container`s cap. Certain products may require to ship with dry ice and additional dry ice fee may apply.

MBS949393 is a recombinant protein targeting FHIT. Also known as Recombinant Human Bis(5'-adenosyl)-triphosphatase. Host: E Coli.